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Home > Health Conditions > Diabetes > SGLT2 inhibitors

SGLT2 inhibitors

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  • Dapagliflozin's HFpEF Benefit Recasts Heart Failure Treatment: DELIVER - Medscape, 8/27/22 - "A key finding of DELIVER, confirmed in several combined analyses also reported at the congress, was that the benefit of dapagliflozin treatment extended to patients with HFpEF in the highest ranges of ejection fraction ... Combined analysis of the DELIVER results with the findings from DAPA-HF in a prespecified analysis that included a total of 11,007 patients with heart failure across the full spectrum of ejection fraction values (with individual patients having values as low as less than 20% or as high as more than 70%) showed a consistent benefit from dapagliflozin treatment for significantly reducing the combined endpoint of cardiovascular death or hospitalization for heart failure by about 22%, compared with placebo, across the complete range of this ejection fraction continuum ... A second, prespecified combined analysis coupled the DELIVER findings with the results of a prior large trial that assessed empagliflozin in patients with HFpEF, EMPEROR-Preserved, which had shown similar findings but with an apparent diminishment of activity in patients at the highest range of preserved left ventricular function, with ejection fractions in excess of about 65%, a tail-off of effect not seen in DELIVER ... SGLT2 inhibitors are the bedrock of therapy for heart failure regardless of ejection fraction or care setting" - See dapagliflozin at reliablerxpharmacy.com.
  • SGLT2 Inhibitors Cut AFib Risk in Real-Word Analysis - Medscape, 6/14/22 - "But despite documentation like this, real-world evidence also continues to show limited uptake of SGLT2 inhibitors in U.S. patients with type 2 diabetes. Records from more than 1.3 million patients with type 2 diabetes managed in the Veterans Affairs Healthcare System during 2019 or 2022 documented that just 10% of these patients received an agent from this class, even though all were eligible to receive it, according to findings in a separate report at the meeting ... The study's primary endpoint was the incidence of hospitalization for AFib, which occurred a significant 18% less often in the patients who started on an SGLT2, compared with those who started a DPP4 inhibitor during median follow-up of 6.7 months, and a significant 10% less often, compared with those starting a GLP-1 receptor agonist during a median follow-up of 6.0 months ... in an analysis of more than 130,000 matched pairs, treatment with empagliflozin was linked to a significant 30% reduction in the incidence of hospitalization for heart failure, compared with patients treated with a GLP-1 receptor agonist. Analysis of more than 116,000 matched pairs of patients showed that treatment with empagliflozin linked with a significant 29%-50% reduced rate of hospitalization for heart failure, compared with matched patients treated with a DPP4 inhibitor" - See empagliflozin inhousepharmacy.vu.
  • Dapagliflozin Early Benefit Explored in Reduced-EF Heart Failure - Medscape, 6/6/22 - "Functional capacity in heart failure with reduced ejection fraction (HFrEF) appears to improve within a few weeks of SGLT2-inhibitor initiation, suggests a small, randomized study that followed peak VO2 in patients with HFrEF assigned to take dapagliflozin (Farxiga). The benefit observed at 30 days held at a plateau for at least a few more months ... The new study, called DAPA-VO2 , has limitations but is consistent with a similar study of empagliflozin (Jardiance), investigators observed, and could help explain why clinical risk fell off so rapidly once patients started on SGLT2 inhibitors in major HFrEF trials of these drugs ... Peak VO2 in the study rose 8% further (P = .021) in patients on dapagliflozin compared with placebo a month into the trial, the gain persisting at least to 90 days"
  • SGLT-2 inhibitors as First-Line Therapy in Type 2 Diabetes? - Medscape, 5/23/22 - "only two SGLT-2 inhibitors, canagliflozin and empagliflozin, were shown to have a statistically significant association with decreased major adverse cardiovascular events ... In contrast, neither dapagliflozin nor ertugliflozin showed significant benefit regarding those outcomes ... those four major SLGT-2 inhibitor cardiovascular outcomes trials were placebo-controlled rather than head-to-head trials in which they were compared to an active comparator such as metformin ... The majority of patients were followed for a year or less. This is probably sufficient to assess the impact of some pharmacological mechanisms, for example, the beneficial impact to decrease risk of heart failure by promoting urinary sodium excretion. However, it's probably insufficient time to observe a beneficial impact on atherosclerosis. For example, there is typically a lag of several years before statins demonstrate efficacy with respect to adverse cardiovascular events ... Incidence rates per 1000 person-years for the composite of hospitalization for MI, hospitalization for ischemic or hemorrhagic stroke, or all-cause mortality (MI/stroke/mortality) were 15.0 vs 16.2 for SLGT-2 inhibitors vs metformin, not a significant difference (hazard ratio [HR], 0.96) ... However, for the composite of heart failure hospitalization or all-cause mortality, the rates were 18.3 vs 23.5, a significant difference, with an HR of 0.80. The benefit was seen beginning at about 6 months ... Compared with metformin, SGLT-2 inhibitors showed a significantly lower risk for heart failure hospitalization (HR, 0.78), a numerically (but not significantly) lower risk for MI (HR, 0.70), and similar risks for stroke, mortality, and MI/stroke/HHF/mortality ... Metformin is considerably less costly than any of the SGLT-2 inhibitors ― roughly $10 to $20 per month, compared to more than $500 a month" - See empagliflozin inhousepharmacy.vu.
  • Accelerated and personalized therapy for heart failure with reduced ejection fraction - Eur Heart J 2022 Apr 25 - "The optimal alternative sequences included sodium-glucose cotransporter 2 inhibition and a mineralocorticoid receptor antagonist as the first two therapies" - See empagliflozin inhousepharmacy.vu.
    • Mineralocorticoid Receptor Antagonists for Treatment of Hypertension and Heart Failure - Methodist Debakey Cardiovasc J. 2015 Oct-Dec - "Spironolactone and eplerenone are both mineralocorticoid-receptor antagonists. These compounds block both the epithelial and nonepithelial actions of aldosterone, with the latter assuming increasing clinical relevance. Spironolactone and eplerenone both affect reductions in blood pressure either as mono- or add-on therapy; moreover, they each afford survival benefits in diverse circumstances of heart failure and the probability of renal protection in proteinuric chronic kidney disease. However, as use of mineralocorticoid-blocking agents has expanded, the hazards inherent in taking such drugs have become more apparent. Whereas the endocrine side effects of spironolactone are in most cases little more than a cosmetic annoyance, the potassium-sparing effects of both spironolactone and eplerenone can prove disastrous, even fatal, if sufficient degrees of hyperkalemia emerge. For most patients, however, the risk of developing hyperkalemia in and of itself should not discourage the sensible clinician from bringing these compounds into play. Hyperkalemia should always be considered a possibility in patients receiving either of these medications; therefore, anticipatory steps should be taken to minimize the likelihood of its occurrence if long-term therapy of these agents is being considered"
    • Spironolactone - dermcoll.edu.au - "Spironolactone is an anti-male hormone (anti-androgen) medication. It blocks the male hormone receptor and reduces the level of the male hormones, testosterone and DHEAS ... Spironolactone has a diuretic (“fluid tablet”) effect and increases urine production. This medication lowers blood pressure and reduces fluid retention seen in conditions such as heart failure and chronic liver disease. Spironolactone can be used to treat low potassium levels (hypokalaemia)" - Note: Lowering testosterone sounds like it would do more harm then good. I can cite studies to back if up. Maybe what needs to be lowered is SHBG:
    • Sex hormone-binding globulin: a new marker of disease severity and prognosis in men with chronic heart failure - Rev Esp Cardiol 2009 Dec - "Sex hormone-binding globulin (SHBG) is a key regulator of the actions of anabolic steroids. Chronic heart failure (HF) has been associated with anabolic steroid deficiency, but its relationship with SHBG is not known ... At enrolment, the SHBG level (median 34.5 nmol/L, IQR 27-50 nmol/L) was correlated with the N-terminal probrain natriuretic peptide level (r=0.271, P=.005), LVEF (r=-0.263, P=.007), body mass index (r=-0.199, P=.020) and total testosterone level (r=0.332, P=.001). The median SHBG level was higher in the 16 patients (15.4%) who died, at 48.5 nmol/L (IQR 36-69.5 nmol/L) vs. 33 nmol/L (IQR 25.3-48.7 nmol/L; P=.001), and a high level was associated with an increased risk of death (hazard ratio [HR]=1.045, 95% confidence interval [CI] 1.021-1.069; P< .001). The association remained significant after adjustment in Cox multivariate regression modeling, at HR=1.049 (95% CI 1.020-1.079; P=.001). Analysis by SHBG tertiles showed mortality was 30% in the third tertile, 14% in the second, and 4% in the first (log rank 0.007; HR=3.25 ... The SHBG level correlated with measures of HF severity and was associated with a higher risk of cardiac death"
  • Empagliflozin Rapidly Improves Acute Heart Failure Symptoms in Hospitalized Patients - Medscape, 4/14/22 - "The trial randomized patients hospitalized for acute heart failure after a brief period of stabilization regardless of their left ventricular ejection fraction or presence of diabetes to receive a single, daily dose of 10 mg of empagliflozin (Jardiance) or placebo starting a median of 3 days after admission ... Using a “win ratio” method for analyzing the composite endpoint, the primary analysis showed that treatment with empagliflozin for 90 days boosted the win ratio by a significant 36% relative to placebo (Nature Med. 2022 Mar;28[3]: 568-74) ... EMPULSE is the second trial to show that an SGLT2 inhibitor can safely and effectively treat patients hospitalized for acute heart failure. Previously, results from the SOLOIST-WHFpivotal trial, which enrolled 1,222 patients with type 2 diabetes recently hospitalized for worsening heart failure, showed that treatment with an investigational, combined SGLT2 and SGLT1 inhibitor, sotagliflozin, resulted in a significant, 33% relative reduction in the primary outcome compared with placebo after a median 9 months of treatment."
  • Heart Failure With Preserved Ejection Fraction: New Treatments Provide 'Hope' - Medscape, 3/28/22 - "That is, those individuals in PARAGON-HF who had ejection fractions slightly on the lower end of "normal" tended to benefit more from this medication as well. That differentiated by sex. This is a controversial aspect of the field and it is something that's evolving on a day-to-day or month-to-month basis ... Sacubitril-valsartan, I think, would be a medicine that could be of particular benefit in this patient. That was the first of the next few trials in HFpEF that started to yield potential new drug classes for HFpEF. ... The next drug class is one with which all aspects of cardiology have become more and more aware, and the HFpEF field is no stranger. With the results of the EMPEROR-Preserved trial we have, in the history of HFpEF clinical trials, our first positive trial, and a monumental moment. A trial evaluating the efficacy of empagliflozin (a sodium-glucose cotransporter 2 [SGLT2] inhibitor) vs placebo in HFpEF. This is the ideal patient who may benefit from this medicine ... EMPEROR-Preserved demonstrated a reduction in a composite endpoint of heart failure hospitalization and cardiovascular death. As you mentioned, Clyde, this efficacy was driven by a reduction in heart failure hospitalization. The class of SGLT2 inhibitors would be, certainly, a medicine that would provide much benefit not only from a reduction in heart failure hospitalization perspective, but a marked improvement in symptoms" - See empagliflozin at ihouseepharmacy.
  • SGLT2 Inhibitors May Cut Repeat Syncope in Type 2 Diabetes - Medscape, 2/16/22 - "vaso-vagal syncope (VVS) ... Patients treated with an SGLT2 inhibitor at entry had a significant (45%) reduction in their incidence of VVS during 1-year follow-up compared with the patients not on SGLT2 inhibitor treatment in a Cox multiple regression analysis that included multiple potential demographic and clinical confounders, including age, smoking status, body mass index, heart rate, and beta blocker use" - See empagliflozin at ihouseepharmacy.
    • What to know about vasovagal syncope - medicalnewstoday.com - "The term vasovagal syncope (VVS) describes fainting that occurs in response to a sudden drop in heart rate or blood pressure. The resulting lack of blood and oxygen to the brain is what causes a person to pass out"
  • US Underuse of GLP-1RA, SGLT-2i in Type 2 Diabetes Persists - Medscape, 2/15/22 - "Only 11% to 14% of US adults with type 2 diabetes received treatment with a glucagon-like peptide-1 receptor agonist (GLP-1RA) or with a sodium glucose cotransporter-2 (SGLT2) inhibitor from 2018 to 2020 despite clear indications for their use ... Why This Matters ... Agents from both the GLP-1RA and SGLT-2 inhibitor classes confer protection against major atherosclerosis-based adverse cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD). SGLT-2 inhibitors also lower the risk of hospitalization for heart failure and prevent worsening kidney function in patients with type 2 diabetes and ASCVD risk or with diabetic kidney disease"
  • SGLT2 Inhibitors in Older Adults with Heart Failure with Preserved Ejection Fraction - Drugs Aging 2022 Feb 4 - "Until now, empagliflozin is the first therapy that has convincingly been shown to improve clinical outcome in HFpEF. Importantly, some key points should be considered to better understand the impact of empagliflozin on the patient trajectory, particularly in older adults with HFpEF. In this current opinion article, we have therefore provided more information on how to translate the findings of the EMPEROR-Preserved trial to the setting of older adults, with a focus on the impact of empagliflozin on hospitalizations, both heart failure-related and all-cause. To better understand the importance of EMPEROR-Preserved findings, we compared these findings with previous relevant HFpEF and heart failure with reduced ejection fraction (HFrEF) trials and provided information on ongoing trials in the HFpEF setting" -  See empagliflozin at ihouseepharmacy.
  • Primary Prevention of Cardiovascular and Heart Failure Events With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Their Combination in Type 2 Diabetes - Diabetes Care 2022 Jan 31 - "major adverse cardiac and cerebrovascular events (MACCE) and heart failure (HF) ... SGLT2i and SGLT2i/GLP-1RA combination regimens may be beneficial in primary prevention of MACCE and HF and GLP-1RA for HF"
  • Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors and Risk of Nonalcoholic Fatty Liver Disease Among Patients With Type 2 Diabetes - Diabetes Care 2022 Feb 1 - "To determine whether glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors, separately, are associated with a decreased risk of nonalcoholic fatty liver disease (NAFLD) compared with dipeptidyl peptidase 4 (DPP-4) inhibitors among patients with type 2 diabetes ... SGLT-2 inhibitors, and possibly GLP-1 RA, may be associated with a decreased incidence of NAFLD and hepatic transaminase elevation among patients with type 2 diabetes"
  • SGLT2 in Patients With Type 2 Diabetes Lowers Risk of Gout - Medscape, 2/8/22 - "During a median 5.6-year follow-up, treatment with an SGLT2 inhibitor was associated with a 54% (P < .0001) lower rate of incident gout and a 62% (P < .0001) lower rate of all-cause mortality compared with DDP4 inhibitors in propensity-score matched groups in a multivariable Cox analysis, after adjustment for significant demographics, past comorbidities, other drug use, and subclinical biomarkers"
  • SGLT-2 Inhibitors, GLP1-RAs Show Cardiorenal Event Prevention in Meta-analysis - Medscape, 1/31/22 - "Among three classes of newer antidiabetic drugs, sodium glucose cotransporter-2 (SGLT-2) inhibitors were the most effective for reducing cardiovascular deaths, renal events, and hospitalizations for heart failure (HHF) in patients with or without diabetes"
  • Lower Blood Sugar Levels Extends Lifespan - SGLT2 - Dr. Brad Stanfield, YouTube - See empagliflozin at ihouseepharmacy. Here are the studies discussed in the video:
    • Canagliflozin extends life span in genetically heterogeneous male but not female mice - JCI Insight 2020 Nov 5 - "Cana extended median survival of male mice by 14% ... with parallel effects seen at each of 3 test sites ... Cana led to lower fasting glucose and improved glucose tolerance in both sexes, diminishing fat mass in females only ... Cana is likely to reflect blunting of peak glucose levels, because similar longevity effects are seen in male mice given acarbose, a diabetes drug that blocks glucose surges through a distinct mechanism, i.e., slowing breakdown of carbohydrate in the intestine" - See canagliflozin at inhousepharmacy.vu but from what I've read over the years, empagliflozin is a better SGLT2i. For one thing, it produces twice the blood pressure reduction. See empagliflozin inhousepharmacy.vu.
    • SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials - Lancet 2019 Jan 5 - "systematic review and meta-analysis of randomised, placebo-controlled, cardiovascular outcome trials of SGLT2i in patients with type 2 diabetes ... 34 322 patients ... SGLT2i reduced major adverse cardiovascular events by 11% ... SGLT2i reduced the risk of cardiovascular death or hospitalisation for heart failure by 23% (0·77 [0·71-0·84], p<0·0001), with a similar benefit in patients with and without atherosclerotic cardiovascular disease and with and without a history of heart failure. SGLT2i reduced the risk of progression of renal disease by 45%"
    • Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i) as a Primary Preventative Agent in the Healthy Individual: A Need of a Future Randomised Clinical Trial? - Front Med (Lausanne) 2021 Aug 23 - "SGLT2i used as a monotherapy are all associated with a low risk of developing hypoglycaemia ... clinical trials in China found that SGLT2i monotherapy was not observed with increased hypoglycaemia risk ... The widespread use of SGLT2i in recent years has been associated with a slightly increased risk of diabetic ketoacidosis ... A recent review (55) discussed the indirect mechanism of reno-protective benefit with SGLT2i, which includes reducing hyperglycaemia, lowering blood pressure, decreasing uric acid, promoting weight loss, increasing glucagon level, reducing insulin level and promoting diuresis ... non-diabetic CKD patients and have proved to delay the progression of kidney disease, lower the risk of cardiovascular events and improve survival rates, highlighting their use beyond the scope of only diabetic patients ... BP reduction was observed in Phase III studies with the average 5.5 mmHg decrease in systolic and the average 1.5 mmHg decrease in diastolic BP ... recent review (55) discussed the indirect mechanism of reno-protective benefit with SGLT2i, which includes reducing hyperglycaemia, lowering blood pressure, decreasing uric acid, promoting weight loss, increasing glucagon level, reducing insulin level and promoting diuresis ... Obesity is well established to be an independent risk factor for cardiovascular disease (81). SGLT2i promote weight loss via glycosuria and negative energy balance, thereby leading to significant weight loss ... Taking all the evidences together, there is a need for consideration of SGLT2i as a potential agent for primary prevention clinical trial in low-risk of cardiovascular and renal diseases or even healthy population with research design focusing on ensuring its safety and minimising potential side effects" -
    • A longitudinal assessment of the natural rate of decline in renal function with age - J Nephrol 2014 Dec;27(6):635-41 - "annual rate of decline in eGFR in healthy subjects was 0.97 ± 0.02 ml/min/year/1.73 m(2). This decline increased significantly from 0.82 ± 0.22 in age-group 20-30 years to 0.84 ± 0.08, 1.07 ± 0.08 and 1.15 ± 0.12 ml/min/year/1.73 m(2) in age groups 31-40, 41-50 and 50 years and older respectively"
    • Longer lifespan in male mice treated with a weakly estrogenic agonist, an antioxidant, an α‐glucosidase inhibitor or a Nrf2‐inducer - Aging Cell 2016 Oct;15(5):872-84 "Metformin alone, at a dose of 0.1% in the diet, did not significantly extend lifespan" - See protandim at Amazon.com.
      • Protandim® - Alzheimer's Drug Discovery Foundation - "May be more useful to take the individual antioxidant ingredients at doses associated with therapeutic benefit than this combination which has no clear clinical value ... Protandim® is a patented blend of 5 herbal ingredients with antioxidant activity: milk thistle (Silybum marianum) extract (225 mg), bacopa (Bacopa monnieri) extract (150 mg), ashwagandha (Withania somnifera) root (150 mg), green tea (Camellia sinensis) extract (75 mg), and turmeric (Curcuma longa) extract (75 mg) ... Protandim® chow supplementation (equivalent to human supplement dosage) led to a 7% increase in median survival (p< 0.012) in male mice but had no effect on survival in females or in maximum survival (p=0.1) of either sex"
  • SGLT2 Inhibitors Improve Cardiovascular Outcomes Across Groups - Medscape, 1/6/22 - "The findings, from a meta-analysis of 10 major randomized clinical trials, were published online January 5 in JAMA Network Open by Mukul Bhattarai, MD, a cardiology fellow at the Southern Illinois University School of Medicine, Springfield, Illinois, and colleagues ... Among a total of 71,553 high-risk patients, 39,053 received an SGLT2 inhibitor and 32,500 received a placebo ... The primary outcome of cardiovascular death or hospitalization for heart failure occurred in 8.10% randomized to SGLT2 inhibitors compared with 11.56% in the placebo group, a significant difference with odds ratio 0.67 ... Patients receiving SGLT2 inhibitors also had significantly lower rates of major adverse cardiovascular events, defined as death due to cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Those events occurred in 9.82% vs 10.22%, with an odds ratio of 0.90 ... Hospitalizations and emergency department visits with heart failure were also reduced with SGLT2 inhibitors (4.37% vs 6.81%; odds ratio, 0.67; P < .001), as was cardiovascular death (4.65% vs 5.14%; odds ratio, 0.87" - See empagliflozin inhousepharmacy.vu.
  • SGLT2 Inhibitors in Primary Care: 'All Hands on Deck' for Improving Heart Failure Outcomes - Medscape, 12/23/21 - "SGLT2 inhibitors lower blood sugar concentrations by blocking the reabsorption of glucose by the kidneys. They also at least transiently increase urinary sodium excretion which along with a number of other mechanisms may provide benefits in heart failure ... It often takes years for effective new therapies to reach patients after positive results of clinical trials and inclusion in practice guidelines ... If you are seeing a patient with heart failure that is not on an SGLT2 inhibitor, definitely consider starting so long as there are no prevailing contraindications, and keep their specialists in the loop ... Heart failure patients are going to see various generalists and specialists, so the clinician who should be prescribing SGLT2 inhibitors is whoever has the opportunity to do so" - See dapagliflozin at reliablerxpharmacy.com.  They don't carry empagliflozin.
  • The diabetes medication that could revolutionize heart failure treatment - Science Daily, 12/1/21 - "For many years there was not a single medicine that could improve the outcome in patients with the second type of heart failure -- those patients with preserved ejection fraction ... SGLT2 inhibitors are more commonly known under their trade-names Forxiga (Dapagliflozin), Invokana (Canagliflozin), and Jardiance (Empagliflozin) ... We found that patients taking SGLT2 inhibitors were 22 per cent less likely to die from heart-related causes or be hospitalised for heart failure exacerbation than those taking placebo" - See dapagliflozin at reliablerxpharmacy.com.
  • SGLT2 Inhibitor Use Tied to Fewer Atrial Arrhythmias - Medscape, 12/2/21 - "treatment with an SGLT2 inhibitor was tied to a significant 23% relative reduction in atrial arrhythmia events and a 44% relative drop in all-cause death ... "We think that a reduction in left atrial pressure" produced by treatment with an SGLT2 inhibitor "may be linked to the reduction in atrial arrhythmias." - See dapagliflozin at reliablerxpharmacy.com.

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